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SIRT1 is downregulated by autophagy in senescence and ageing
- Source :
- Nature cell biology, vol 22, iss 10, Nature cell biology
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- SIRT1 (Sir2) is an NAD+-dependent deacetylase that plays critical roles in a broad range of biological events, including metabolism, the immune response and ageing1,2,3,4,5. Although there is strong interest in stimulating SIRT1 catalytic activity, the homeostasis of SIRT1 at the protein level is poorly understood. Here we report that macroautophagy (hereafter referred to as autophagy), a catabolic membrane trafficking pathway that degrades cellular components through autophagosomes and lysosomes, mediates the downregulation of mammalian SIRT1 protein during senescence and in vivo ageing. In senescence, nuclear SIRT1 is recognized as an autophagy substrate and is subjected to cytoplasmic autophagosome–lysosome degradation, via the autophagy protein LC3. Importantly, the autophagy–lysosome pathway contributes to the loss of SIRT1 during ageing of several tissues related to the immune and haematopoietic system in mice, including the spleen, thymus, and haematopoietic stem and progenitor cells, as well as in CD8+CD28- T cells from aged human donors. Our study reveals a mechanism in the regulation of the protein homeostasis of SIRT1 and suggests a potential strategy to stabilize SIRT1 to promote productive ageing.
- Subjects :
- Male
Senescence
Cell Survival
T-Lymphocytes
Inbred C57BL
Medical and Health Sciences
Article
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Sirtuin 1
Downregulation and upregulation
Autophagy
Animals
Humans
Progenitor cell
Cellular Senescence
Cell Proliferation
030304 developmental biology
Cell Nucleus
0303 health sciences
Chemistry
Stem Cells
Autophagosomes
Cell Biology
Middle Aged
Biological Sciences
Cell biology
Mice, Inbred C57BL
enzymes and coenzymes (carbohydrates)
Haematopoiesis
Ageing
030220 oncology & carcinogenesis
Female
NAD+ kinase
biological phenomena, cell phenomena, and immunity
Lysosomes
Microtubule-Associated Proteins
hormones, hormone substitutes, and hormone antagonists
Developmental Biology
Subjects
Details
- ISSN :
- 14764679 and 14657392
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Nature Cell Biology
- Accession number :
- edsair.doi.dedup.....ad2cf4446e5fa5dd1ffb2a316b8adb87